Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), which is characterized by the total absence of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) expression. Cinobufacini injection (CI) is the aqueous extract from the dry skin of Bufo gargarizans, which is broadly used for the treatment of malignant tumors. However, the potential mechanism of CI against TNBC has not been fully revealed. In this study, we found that CI inhibited the proliferation of MDA-MB-231 and 4T1 cells in a time- and dose-dependent manner. RNA-seq data showed that downregulated and upregulated genes were mainly enriched in biological processes related to tumor cell proliferation, including cell cycle arrest and regulation of apoptosis signaling pathways. Indeed, after CI treatment, the protein level of CDK1 and Bcl-2/Bax decreased, indicating that CI induced the cell cycle of MDA-MB-231 arrest in the G2/M phase and increased the rate of apoptosis. Meanwhile, CI significantly inhibited the growth of tumor in vivo, and RNA-seq data showed that the TAZ signaling pathway played a vital role after CI treatment. Both immunohistochemistry and Western blot analysis confirmed the downregulation of Pin1 and TAZ, caused by CI treatment. Furthermore, the bioinformatics analysis indicated that Pin1 and TAZ were indeed elevated in TNBC patients, with poor staging, classification, and patient survival rate. In conclusion, CI effectively inhibited the proliferation of TNBC in vitro and in vivo and induced their apoptosis and cycle arrest through the Pin1–TAZ pathway.
Two years after the coronavirus disease 2019 (COVID-19) outbreak, an increasing number of patients continue to suffer from long COVID (LC), persistent symptoms, and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms. Constant fatigue is one of the most common LC symptoms, leading to severely reduced quality of life among patients. Ginseng Radix et Rhizoma—known as the King of Herbs in traditional Chinese medicine—has shown clinical anti-fatigue effects. In this review, we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds, with a special focus on anti-viral, immune remodeling, endocrine system regulation, and metabolism, suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC, especially in regard to targeting fatigue.
Objective: Our study aimed to investigate the action of Xuanfei Baidu granules (XFBD) and their mechanism of action in a model of coronavirus pneumonia under cold and damp conditions.Methods: A total of 60 Bagg Albino (BALB/c) mice were randomly assigned to different groups, including the control, model, low-dose XFBD (1.84 g/kg), medium-dose XFBD (3.67 g/kg), and high-dose XFBD (7.34 g/kg) groups. To simulate the model of coronavirus infection, a combination of cold and damp stimuli and coronavirus strain 229E (CoV 229E) was employed. Subsequently, XFBD was administered on the fifth day and lasted for 3 days. To evaluate the efficacy of XFBD in BALB/c mice, various parameters, including behavior, lung index, viral load, and pulmonary pathology, were observed. Levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). The fractions of CD4 + T cells, CD8 + T cells, and B cells were measured using flow cytometry.Results: The mice in the control group were active, in good condition, and exhibited shiny hair. After modeling, the mice demonstrated less activity, low energy levels, messy and less shiny hair, poor appetite, and soft stools. The symptoms of coronavirus pneumonia were all significantly improved after the administration of different doses of XFBD. At three dosage levels, XFBD effectively increased gastrin (GAS) content, whereas medium and high doses of XFBD reduced motilin (MTL) content. The high-dose XFBD group showed a significant reduction in pathological damage to lung tissue. Treatment with three doses of XFBD demonstrated significant downregulation of inflammatory factors and regulation of CD4 + and CD8 + T cell and B cell expression. The high-dose XFBD group exhibited enhanced efficacy compared to the other doses.Conclusions: XFBD showed a therapeutic effect on coronavirus pneumonia under cold and damp conditions, improved the behavioral characterization and gastrointestinal index, and reduced the lung virus titer and histopathology. This may be associated with the inhibition of inflammation and an increase in the number of lymphocytes.
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